crossing96/oncoscreening huggingface dataset:
Overexpression of BMAL-1 is related to progression of urothelial carcinoma in arsenic exposure area.	BACKGROUND: Environmental exposure to arsenic has long been associated with various clinical and pathophysiological aspects of urothelial carcinoma (UC), although the role of arsenic in UC and its impact on circadian proteins, particularly BMAL-1, remains unestablished. Previous research suggests that arsenic upregulates Aurora kinase A (AURKA), subsequently inhibiting GSK-3β, which might lead to overexpression of BMAL-1; nevertheless, the underlying pathway and its clinical significance in UC with arsenic exposure have yet to be validated. This study focuses on two potential upstream regulators of BMAL-1, AURKA and GSK-3β. METHODS: Ninety-nine tumor tissue samples were retrospectively collected along with their respective clinical data. Immunohistochemistry was employed to assess the expression of each protein. RESULTS: A positive relationship was observed between the expression levels of AURKA and BMAL-1 (p < 0.001), while negative correlations were noted between the expression levels of GSK-3β and AURKA (p < 0.001), and between GSK-3β and BMAL-1 (p = 0.003). Tissue samples exposed to arsenic exhibited significantly higher levels of AURKA (p < 0.001) and BMAL-1 (p < 0.001), a markedly lower expression of GSK-3β (p = 0.001), alongside a decreased survival status (p = 0.025) compared to non-exposed samples. Furthermore, patients with UC of higher tumor grade tended to show increased levels of AURKA (p < 0.001), BMAL-1 (p < 0.001), and decreased levels of GSK-3β (p < 0.001). Elevated expression of AURKA (p < 0.001) and BMAL-1 (p = 0.002), as well as reduced expression of GSK-3β (p = 0.003), were also associated with a decreased survival status. CONCLUSIONS: This study highlights the differential expression of BMAL-1, AURKA, and GSK-3β in association with arsenic exposure and their significant impact on clinical and pathological features of UC. Moreover, BMAL-1, AURKA, and GSK-3β emerge as potential prognostic markers for UC in regions with arsenic exposure.	bladder
High-risk non-muscle invasive bladder cancer: Outcomes of patients who cannot benefit from standard of care.	INTRODUCTION: High-grade non-muscle invasive bladder cancer (HG-NMIBC) exposes to a high risk of recurrence and progression. Standard of care includes repeated trans-urethral resection of bladder tumor (reTURBT) and bacillus Calmette-Guérin (BCG) therapy. Not following Standard of care (SOC) may be associated with a worse prognosis. We aimed to compare prognosis outcomes of patients with primary HG-NMIBC according to the respect of the SOC or not. MATERIALS AND METHODS: We conducted an eleven-year retrospective observational study including all patients undergoing initial bladder resection for de novo HG-NMIBC at our institution. Exclusion criteria were prior urothelial carcinoma histology, low grade NMIBC or ≥T2 staging. Four groups were formed according to the treatment received. RESULTS: Among 164 patients, 44.5% received standard of care, 18.3% received only BCG-therapy, 16.5% benefited only from reTURBT and 20.7% did not receive treatment. Upstaging to T2 tumor was found in 6% of reTURBT specimens. Presence of residual tumor (RT) on re-TURBT (P<10(-4)) and having benefited from SOC (P=0.016) impacted recurrence-free survival. Progression-free survival was impacted by presence of RT (P=0.001) but not by SOC (P=0.284). CONCLUSION: Performing standard of care on patients with HG-NMIBC is associated with a lower risk of recurrence. We believe SOC should be provided for all HG-NMIBC patients, especially those with poor prognostic factors such as T1 tumor, or multiplicity or largeness of the bladder tumor.	bladder
Robot-Assisted Cystectomy in Patients With Previous Pelvic Irradiation: A Comprehensive Systematic Review and Single-Arm Meta-Analysis.	To evaluate the perioperative outcomes of robot-assisted cystectomy in previous pelvic irradiation patients. We performed a systematic review with a single-arm meta-analysis, searching the PubMed, Embase, Scopus, and Cochrane databases through July 2024. Included studies reported perioperative outcomes of robot-assisted radical cystectomy in patients with prior pelvic irradiation. Extracted data included operative time, blood loss, complication rates (using the Clavien-Dindo classification), readmission rates, and length of hospital stay. Study quality was assessed and a single-arm meta-analysis was conducted to synthesize the data. This systematic review included 150 patients from 4 retrospective studies. The median operative time ranged from 330 to 382 minutes (Overall Mean = 349.50 min; 95% CI, 331-380), and blood loss varied between 264 mL and 495 mL (Overall Mean = 351.50 mL; 95% CI, 264-495). Major complications, defined as Clavien-Dindo grade ≥ III, were reported in 20% to 32% of cases, while total early complications within 90 days ranged from 53% to 59% (Overall rate = 0.58; 95% CI, 0.42-0.75). The readmission rate within 90 days varied between 22% and 40% (Overall rate = 0.31; 95% CI, 0.16-0.47). RARC in patients with prior pelvic irradiation resulted in comparable perioperative outcomes to nonirradiated patients. This review highlights the potential safety and efficacy of RARC in this complex patient group. Future studies comparing surgical approaches with detailed reporting on radiation exposure are essential to validate these findings.	bladder
Hu similarity coefficient: a clinically oriented metric to evaluate contour accuracy in radiation therapy.	To propose a clinically oriented quantitative metric, Hu similarity coefficient (HSC), to evaluate contour quality, gauge the performance of auto contouring methods, and aid effective allocation of clinical resources. The HSC is defined as the ratio of the number of boundary points of the initial contour that doesn't require modifications over the number of boundary points of the final adjusted contour. To demonstrate the clinical utility of the HSC in contour evaluation, we used publicly available pelvic CT data from the Cancer Imaging Archive. The bladder was selected as the organ of interest. It was contoured by a certified medical dosimetrist and reviewed by a certified medical physicist. This contour served as the ground truth contour. From this contour, we simulated two contour sets. The first set had the same Dice similarity coefficient (DSC) but different HSCs, whereas the second set kept a constant HSC while exhibiting different DSCs. Four individuals were asked to adjust the simulated contours until they met clinical standards. The corresponding contour modification times were recorded and normalized by individual's manual contouring times from scratch. The normalized contour modification time was correlated to the HSC and DSC to evaluate their suitability as quantitative metrics assessing contour quality. The HSC maintained a strong correlation with the normalized contour modification time when both sets of simulated contours were included in analysis. The correlation between the DSC and normalized contour modification time, however, was weak. Compared to the DSC, the HSC is more suitable for evaluating contour quality. We demonstrated that the HSC correlated well with the average normalized contour modification time. Clinically, contour modification time is the most relevant factor in allocating clinical resources. Therefore, the HSC is better suited than the DSC to assess contour quality from a clinical perspective.	bladder
[A Case of Secondary Extramammary Paget's Disease Developed at 11 Years after Cystectomy].	An 82-year-old woman previously underwent cystectomy and ureterocutaneous ureteral fistula for bacillus calmette guerin-resistant bladder cancer at the age of 70 years old in February 2012. Pathological examination revealed a pTisN0. In October 2020, the patient experienced vulvar itching and pain, which prompted her to consult a gynecologist. Vulvovaginitis was diagnosed, and the patient was observed. However, in June 2023, the vulvar itching persisted, prompting a biopsy for refractory erosions of the vulva. Paget cells were identified in the epidermis, and immunostaining (CK7 (＋), CK20 (＋), p63 (＋), GATA3 (＋), and GCDFP15 (-)) was used to diagnose secondary extramammary Paget's disease due to urothelial carcinoma. Magnetic resonance imaging revealed a 25 mm mass in the pelvic floor, and a biopsy showed the same immunostaining pattern as the skin lesion. Consequently, a diagnosis of local recurrence 11 years after cystectomy and associated secondary extramammary Paget's disease was established. Owing to the evidence of invasion of the mass into the levator ani muscle, she underwent laparoscopic rectal resection plus combined resection of the tumor, perineum, and levator ani muscle in October. Currently, she is 3 months postoperatively without evidence of recurrence.	bladder
Non-coding RNAs in bladder cancer, a bridge between gut microbiota and host?	In recent years, the role of gut microbiota (GM) in bladder cancer has attracted significant attention. Research indicates that GM not only contributes to bladder carcinogenesis but also influences the efficacy of adjuvant therapies for bladder cancer. Despite this, interventions targeting GM have not been widely employed in the prevention and treatment of bladder cancer, mainly due to the incomplete understanding of the complex interactions between the host and gut flora. Simultaneously, aberrantly expressed non-coding RNAs (ncRNAs) have been frequently associated with bladder cancer, playing crucial roles in processes such as cell proliferation, invasion, and drug resistance. It is widely known that the regulation of GM-mediated host pathophysiological processes is partly regulated through epigenetic pathways. At the same time, ncRNAs are increasingly regarded as GM signaling molecules involved in GM-mediated epigenetic regulation. Accordingly, this review analyzes the ncRNAs that are closely related to the GM in the context of bladder cancer occurrence and treatment, and summarizes the role of their interaction with the GM in bladder cancer-related phenotypes. The aim is to delineate a regulatory network between GM and ncRNAs and provide a new perspective for the study and prevention of bladder cancer.	bladder
ZC3H13 promotes autophagy in bladder cancer through m6A methylation modification of PJA2 and ubiquitination of KSR1.	The N6-methyladenine (m6A) modification is the most common modification of messenger RNAs in eukaryotes and has crucial roles in multiple cancers, including bladder cancer (BLCA). This paper aimed to probe the molecular mechanism of zinc-finger CCCH-type containing 13 (ZC3H13)-mediated N6-methyladenine (m6A) modification in BLCA progression via autophagy. Differential expression of ZC3H13 in BLCA was analyzed by the bioinformatics database. ZC3H13 expression in BLCA tissues and cell lines was determined, and malignant behaviors of BLCA cells were examined in vitro and in vivo. ZC3H13 was decreased in BLCA tissues and cell lines relative to adjacent tissues and normal uroepithelial cells. ZC3H13 overexpression restricted BLCA cell growth in vitro and curbed BLCA development in vivo. ZC3H13 promoted the mRNA stability of paraja ring finger 2 (PJA2) through m6A modification, leading to the ubiquitination degradation of the kinase suppressor of Ras 1 (KSR1). Knockdown of PJA2 and overexpression of KSR1 reversed the inhibitory effect of ZC3H13 on BLCA progression. ZC3H13 degraded KSR1 through m6A modification of PJA2, promoted cell autophagy, and repressed BLCA progression. Overall, ZC3H13 promotes the mRNA stability of PJA2 through m6A modification to degrade KSR1, thereby promoting autophagy in BLCA.	bladder
Sulfasalazine-loaded nanoframes: A new frontier in bladder cancer therapy through ferroptosis induction.	Promoting ferroptosis in tumor cells has emerged as a promising strategy for cancer therapy. Nonetheless, the heightened antioxidant activity within tumor cells hampers this approach, diminishing its effectiveness and fostering drug resistance. In this study, a new type of sulfasalazine (SAS) loaded nanoframe self-etched Pt-Co nanodendrites (Pt/Co-BNN@SAS) was developed, presenting a novel avenue for inducing ferroptosis in tumor cells by depleting glutathione (GSH) for cancer treatment. Pt/Co-BNN exhibits notable peroxidase (POD) activity, catalyzing the production of abundant oxygen radicals through the consumption of hydrogen peroxide (H(2)O(2)) and the concurrent depletion of GSH. Simultaneously, the liberated sulfasalazine (SAS) from Pt/Co-BNN@SAS effectively obstructs system xc(-), impeding the absorption of cystine by tumor cells and thereby expediting GSH depletion. The expeditious reduction of GSH markedly stimulates the accumulation of lipid peroxides (LPO) and suppresses glutathione peroxidase 4 (GPX4), consequently triggering ferroptosis in bladder cancer cells and inhibiting the migration ability of bladder cancer cells effectively. This research contributes to a more profound comprehension of nano-drug-biological interactions and provides a prospective outlook on treating bladder cancer by instigating ferroptosis in tumor cells through GSH depletion.	bladder
E2F8 facilitates malignant phenotypes of muscle-invasive bladder cancer via increasing MCM7 expression.	E2F transcription factor 8 (E2F8) is an important regulator of the cell cycle. In this study, we first assessed the expression of E2F8 in bladder cancer and examined its effects in the malignant phenotypes of bladder cancer cell lines. We found that E2F8 was upregulated in bladder cancer tissues, and the increased expression was positively associated with higher clinical stage. E2F8 knockdown suppressed bladder cancer cell proliferation, accompanied by the performance of G1 phase arrest and the upregulated Cyclin D1 protein expression. The migrative and invasive capability was reduced in E2F8-depleted bladder cancer cells. Cisplatin resistance is an important cause of bladder cancer relapse. E2F8 downregulation facilitated cisplatin-induced apoptosis of bladder cancer cells. MCM7 is regulated by E2F and has been shown to participate in bladder cancer. There was a positive correlation between E2F8 and MCM7 expression in bladder cancer. We confirmed that E2F8 bound to the promoter region of MCM7 and activated MCM7 transcription. MCM7 overexpression abrogated the suppressive effects of E2F8 knockdown on malignant phenotypes of bladder cancer cells. We also demonstrated that E2F8 knockdown suppressed bladder cancer progression in vivo. In conclusion, we verify that E2F8 functioned in bladder cancer, and might exert its function via MCM7.	bladder
Use of 3' Rapid Amplification of cDNA Ends (3' RACE)-Based Targeted RNA Sequencing for Profiling of Druggable Genetic Alterations in Urothelial Carcinomas.	Targeted treatment of advanced or metastatic urothelial carcinomas (UCs) requires the identification of druggable mutations. This study describes the development of a 3' Rapid Amplification of cDNA Ends (3' RACE)-based targeted RNA sequencing panel which accounts for the status of all genes relevant to UC treatment, namely, FGFR1-4, KRAS, NRAS, BRAF, ERBB2 (HER2), CD274 (PD-L1) and PIK3CA. FGFR2/3-activating point mutations or fusions were found in 54/233 (23.2%) tumors. FGFR3 rearrangements were identified in 11 patients, with eight of them being undetectable by commonly used PCR kits. In addition, one tumor contained a high-copy FGFR2 gene amplification accompanied by strong overexpression of the gene. Mutations in RAS/RAF genes were present in 30/233 (12.9%) UCs and were mutually exclusive with alterations affecting FGFR2/3 genes. On the contrary, activating events in the HER2 oncogene (point mutations and overexpression), as well as PIK3CA mutations, which were relatively common, occurred with similar frequencies in RAS/RAF- or FGFR2/3-positive vs. negative samples. High PD-L1 mRNA expression was associated with advanced disease stage and was not observed in tumors with increased HER2 mRNA expression or in UCs with evidence for FGFR2/3 activation. Three of the studied carcinomas had high-level microsatellite instability (MSI). Overall, more than half of the UCs had potentially druggable genetic alterations. The proposed NGS panel permits comprehensive and cost-efficient analysis of UC-specific molecular targets and may be considered in clinical routine.	bladder
Urothelial Urinary Bladder Cancer Is Characterized by Stage-Dependent Aberrations in Metabolism of Bioactive Sphingolipids.	Although dysregulated sphingolipid metabolism was observed in many malignant tumors, bladder cancer has not yet been examined in this regard. This study aims to investigate the metabolism of bioactive sphingolipids across different stages of urothelial urinary bladder cancer (UBC). Forty-eight patients with UBC were included in this study. The neoplasms were classified as either non-muscle-invasive (NMIBC, n = 24) or muscle-invasive (MIBC, n = 24). Samples of the healthy bladder tissue were taken from the patients who underwent radical cystectomy. The content of sphingolipids was measured using an HPLC method, and the mRNA expression of sphingolipid transporters and metabolizing enzymes was evaluated using RT-PCR. Compared to the healthy bladder tissue, the UBC, regardless of the stage, showed an elevated expression of SphK1, Spns2, and ABCC1. The changes in the level of bioactive sphingolipids were strongly stage-dependent. MIBC showed accumulation of sphingosine-1-phosphate (S1P) and ceramide, whereas the content of these sphingolipids in the NMIBC tumor was not different from that of healthy tissue. Moreover, MIBC, compared to NMIBC, was characterized by higher levels of sphingosine and dihydroceramide. We conclude that profound alterations in sphingolipid metabolism develop upon UBC transition from non-muscle-invasive to muscle-invasive. They include the accumulation of S1P, resulting from the increased availability of sphingosine generated from ceramide, which also builds up due to a further activation of its de novo synthesis. We hypothesize that the dysregulation of S1P metabolism leading to the accumulation of this tumor-promoting sphingolipid contributes to the progression of UBC.	bladder
The efficacy of sequential intravesical gemcitabine and docetaxel versus BCG for the treatment of European association of urology very-high risk non-muscle invasive bladder cancer.	BACKGROUND: The European Association of Urology (EAU) recommends early radical cystectomy (RC) for very-high-risk (VHR) nonmuscle invasive bladder cancer (NMIBC), in part due to suboptimal efficacy from BCG in this setting. Effective bladder-sparing alternatives are needed. We compared the oncological outcomes of Gemcitabine/Docetaxel (Gem/Doce) to BCG therapy in patients with VHR NMIBC. METHODS: Retrospective analysis of oncological outcomes in 129 treatment naïve VHR NMIBC patients receiving intravesical Gem/Doce (n = 65) was compared to BCG (n = 64) using Cox regression. RESULTS: Recurrence-free survival (RFS) at 12- and 24-months was 63% and 54% for BCG compared to 79% and 73% for Gem/Doce. Progression-free survival (PFS) at 24-months for BCG was 88% compared to 97% for Gem/Doce. Gem/Doce showed a decreased risk of tumor recurrence compared to BCG (hazard ratio, 0.55; 95% confidence interval, 0.30-0.99; P = 0.05). Moreover, patients in the Gem/Doce group were less prone to discontinue therapy (3.1% vs. 14.1%; P = 0.03). CONCLUSIONS: Gem/Doce provides a level of efficacy in terms of RFS and PFS at least as good as BCG for treatment naïve VHR NMIBC. Prospective validation is needed.	bladder
Standard or Extended Lymphadenectomy for Muscle-Invasive Bladder Cancer.	BACKGROUND: Whether extended lymphadenectomy is associated with improved disease-free and overall survival, as compared with standard lymphadenectomy, among patients with localized muscle-invasive bladder cancer undergoing radical cystectomy is unclear. METHODS: We randomly assigned, in a 1:1 ratio, patients with localized muscle-invasive bladder cancer of clinical stage T2 (confined to muscle) to T4a (invading adjacent organs) with two or fewer positive nodes (N0, N1, or N2) to undergo bilateral standard lymphadenectomy (dissection of lymph nodes on both sides of the pelvis) or extended lymphadenectomy involving removal of common iliac, presciatic, and presacral nodes. Randomization was performed during surgery and stratified according to the receipt and type of neoadjuvant chemotherapy, tumor stage (T2 vs. T3 or T4a), and a Zubrod's performance-status score (0 or 1 vs. 2; assessed on a 5-point scale, with higher scores indicating greater disability). The primary outcome was disease-free survival. Overall survival and safety were also assessed. RESULTS: Of 658 patients who were enrolled, 592 eligible patients were randomly assigned to undergo extended lymphadenectomy (292 patients) or standard lymphadenectomy (300). Surgery was performed by 36 surgeons at 27 sites in the United States and Canada. Neoadjuvant chemotherapy had been received by 57% of the patients. At a median follow-up of 6.1 years, recurrence or death had occurred in 130 patients (45%) in the extended-lymphadenectomy group and in 127 (42%) in the standard-lymphadenectomy group, and the estimated 5-year disease-free survival was 56% and 60%, respectively (hazard ratio for recurrence or death, 1.10; 95% confidence interval [CI], 0.86 to 1.40; P = 0.45). Overall survival at 5 years was 59% in the extended-lymphadenectomy group and 63% in the standard-lymphadenectomy group (hazard ratio for death, 1.13; 95% CI, 0.88 to 1.45). Adverse events of grade 3 to 5 occurred in 157 patients (54%) in the extended-lymphadenectomy group and in 132 (44%) in the standard-lymphadenectomy group; death within 90 days after surgery occurred in 19 patients (7%) and 7 patients (2%), respectively. CONCLUSIONS: As compared with standard lymphadenectomy, extended lymphadenectomy did not result in improved disease-free or overall survival among patients with muscle-invasive bladder cancer undergoing radical cystectomy and was associated with higher perioperative morbidity and mortality. (Funded by the National Cancer Institute and the Canadian Cancer Society; SWOG S1011 ClinicalTrials.gov number, NCT01224665.).	bladder